Device and method for treating obstructive sleep apnea

ABSTRACT

A device and method are provided for treating obstructive respiratory events by electrically stimulating tissue associated with the phrenic nerve or diaphragm to elicit a respiratory response.

RELATED APPLICATION DATA

This application is a continuation in part of U.S. application Ser. No.10/966,484 filed Oct. 15, 2004; U.S. application Ser. No. 10/966,474,filed Oct. 15, 2004; U.S. application Ser. No. 10/966,421, filed Oct.15, 2004; and U.S. application Ser. No. 10/966,472 filed Oct. 15, 2004which are continuations in part of U.S. application Ser. No. 10/686,891filed Oct. 15, 2003 entitled: BREATHING DISORDER DETECTION AND THERAPYDELIVERY DEVICE AND METHOD.

FIELD OF THE INVENTION

This invention relates to a device and method for treating respiratoryand related disorders.

BACKGROUND OF THE INVENTION

There are several factors believed to contribute to the occurrence ofobstructive respiratory events including anatomical deficiencies,deformities or conditions that increase the likelihood or occurrence ofupper airway collapse; ventilatory instability; and fluctuations in lungvolumes. There is believed to be a relationship between lung volume andthe aperture of the upper airway with larger lung volume leading togreater upper airway patency.

Some obstructive sleep apnea (OSA) patients have increased upper airwayresistance and collapsibility that may contribute to vulnerability toobstructive respiratory events. The pharyngeal airway is not supportedby bone or cartiligenous structure and accordingly relies on contractionof the upper airway dilator muscles to maintain patency. The pharyngealairway represents a primary site of upper airway closure.

Some OSA therapy has been based on a belief that OSA results from thesize and shape of the upper airway muscles or conditions such as obesitythat create a narrowing of the upper air passageway and a resultingpropensity for its collapse.

In patients with obstructive sleep apnea, various treatment methods anddevices have been used with very limited success.

CPAP machines have been used to control obstructive sleep apnea bycreating a continuous positive airway pressure (CPAP) at night. Externalventilatory control has been proposed including sensors that sense acessation of breathing to determine when an obstructive sleep apneaevent is occurring.

An implantable stimulator that stimulates the hypoglossal nerve aftersensing an episode of obstructive sleep apnea has been proposed but hasfailed to provide satisfactory results in OSA patients.

Treating OSA has primarily relied on continuous treatment or detectionof an obstructive respiratory event when it is occurring, i.e., when theupper air passageway has closed.

Drug therapy has not provided satisfactory results.

In central sleep apnea, as opposed to obstructive sleep apnea, it hasbeen proposed to stimulate a patient's diaphragm or phrenic nerve toinduce breathing where there is a lack of central respiratory drive.However, such therapy has be contraindicated for obstructive sleep apneaor respiratory events where there is an obstructive component, at leastin part because stimulating a patient to breathe when the airway isobstructed is believed to further exacerbate the collapsing of theairway passage by creating a pressure that further closes the airway.

Accordingly, it would be desirable to provide an improved device andmethod for treating OSA.

It would also be desirable to provide treatment for various otherrespiratory and related disorders.

SUMMARY OF THE INVENTION

The present invention provides a novel approach to treating obstructivesleep apnea and other respiratory related disorders or conditions.

In accordance with one aspect of the invention, in a patient diagnosedwith obstructive sleep apnea, tissue associated with the diaphragm orphrenic nerve is electrically stimulated to prevent obstructiverespiratory events.

In accordance with one aspect of the invention stimulation of thediaphragm or phrenic nerve is provided to such obstructive sleep apneapatients to reduce the occurrence of upper airway collapse or upperairway flow limitation.

In accordance with one aspect of the invention, a device and method forincreasing functional residual capacity (i.e., end expiratory lungvolume) is provided.

In accordance with one aspect of the invention, a device and method forincreasing upper airway patency is provided.

In accordance with one aspect of the invention, a device and method areprovided for providing ventilatory stability in an obstructive sleepapnea patient.

In accordance with one aspect of the invention, an indicator of animpending obstructive respiratory event is detected prior to eventonset.

In accordance with one aspect of the invention, a method for mitigating(i.e., preventing or lessening) obstructive respiratory events isprovided.

In accordance with one aspect of the invention, a method and device isprovided for synchronizing stimulation with one or more portions of anintrinsic breathing cycle.

In accordance with one aspect of the invention, a device and method foreliciting deep inspiration while avoiding airway closure are provided.

In accordance with one aspect of the invention, a device and method fornormalizing peak flow while increasing tidal volume are provided.

In accordance with one aspect of the invention, a device and method formanipulating exhalation are provided.

In accordance with one aspect of the invention, a device and method forentraining breathing are provided.

In accordance with another aspect of the invention, a device detectswhen an obstruction has occurred to a particular extent and refrainsfrom stimulating if the collapse has occurred to a particular extent.

In accordance with another aspect of the invention, a low level ofstimulation is provided for therapeutic effects.

In accordance with another aspect of the invention, a low level ofstimulation to the diaphragm or phrenic nerve is provided through orafter airway closure to speed up airway opening and reduce arousal.

These and other inventions are described herein and/or set forth in theclaims herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a device implanted in a subject inaccordance with the invention.

FIG. 2 is a schematic illustration of a processor unit of a sleepbreathing disorder treatment device in accordance with the invention.

FIG. 3 is a schematic illustration of an external device of a stimulatorin accordance with the invention.

FIG. 4A is a schematic illustration of respiration of an exemplaryobstructive sleep apnea patient as the patient is going into anobstructive sleep apnea event.

FIG. 4B is a schematic illustration of respiration of an exemplaryobstructive sleep apnea patient as the patient is going into anobstructive sleep apnea event.

FIGS. 4C and 4D are schematic illustrations respectively of respirationresponse and stimulation waveforms illustrating a stimulation methodusing a stimulation device according to the invention in which theobstructive sleep apnea event illustrated in FIG. 4A is treated withdeep inspiration stimulation.

FIG. 5A is a schematic illustration of respiration of an exemplaryobstructive sleep apnea patient as the patient is going into anobstructive sleep apnea event.

FIGS. 5B and 5C are schematic illustrations respectively of respirationresponse and stimulation waveforms illustrating a stimulation methodusing a stimulation device according to the invention in which theobstructive sleep apnea event illustrated in FIG. 5A is treated withdeep inspiration stimulation.

FIGS. 6A, 6B and 6C are schematic illustrations respectively of airflow,tidal volume and corresponding stimulation waveforms illustrating astimulation method using a stimulation device according to the inventionin which stimulation is applied during a portion of the respirationcycles.

FIGS. 7A and 7B are schematic illustrations respectively of tidal volumeand corresponding stimulation waveforms illustrating a stimulationmethod using a stimulation device according to the invention in whichstimulation is applied during a portion of the respiration cycles.

FIGS. 8A and 8B are schematic illustrations respectively of tidal volumeand corresponding stimulation waveforms illustrating a stimulationmethod using a stimulation device in which stimulation is applied inaccordance with the invention.

FIGS. 9A, 9B and 9C are schematic illustrations respectively of airflow,tidal volume and corresponding stimulation waveforms illustrating astimulation method using a stimulation device in which stimulation isapplied in accordance with the invention.

FIGS. 10A, 10B and 10C are schematic illustrations respectively ofairflow, tidal volume and corresponding stimulation waveformsillustrating a stimulation method using a stimulation device in whichstimulation is applied in accordance with the invention.

FIGS. 11A and 11B are schematic illustrations respectively ofrespiration response and stimulation waveforms illustrating astimulation method using a stimulation device according to theinvention.

FIGS. 12A, 12B and 12C are schematic illustrations respectively of flowand tidal volume respiration response and stimulation waveformsillustrating a stimulation method using a stimulation device accordingto the invention.

FIGS. 13A and 13B are schematic illustrations respectively ofrespiration response and stimulation waveforms illustrating astimulation method using a stimulation device according to theinvention.

FIGS. 14A and 14B are schematic illustrations respectively ofrespiration response and stimulation waveforms illustrating astimulation method using a stimulation device according to theinvention.

FIG. 15 is a flow chart illustrating operation of a device in accordancewith the invention.

FIG. 16A is a schematic of a signal processor of the processor unit inaccordance with the invention.

FIG. 16B is a schematic example of a waveform of an integrated signalprocessed by the signal processor of FIG. 16A.

FIG. 16C is a schematic EMG envelope waveform.

FIG. 16D is a schematic waveform corresponding to or correlated with airflow.

DETAILED DESCRIPTION

In accordance with one aspect of the invention, a method and device fortreating obstructive sleep apnea patients is provided. According to oneembodiment, a device is provided that manipulates breathing according toone or more protocols, by stimulating the diaphragm or phrenic nerve tomitigate or prevent obstructive respiratory events including obstructivesleep apnea or other events with an obstructive component. The devicemay comprise a phrenic nerve or diaphragm stimulator and a sensorconfigured to sense a condition of a subject indicating a possibilitythat an obstructive respiratory event will occur or is occurring. Inaccordance with the invention, obstructive respiratory events arecharacterized by a narrowing of the air passageway, typically the upperair passageway. Examples of obstructive respiratory events include butare not limited to obstructive sleep apnea, obstructive hypopnea andother respiratory events with an obstructive component.

In another embodiment, stimulation is applied at a low level through orafter an obstructive respiratory event has occurred.

In addition, in accordance with the invention stimulation techniques forcontrolling or manipulating breathing may be used for therapeuticpurposes in other non-OSA patients.

FIGS. 1 and 2 illustrate a stimulator 20 comprising electrode assemblies21, 22, each comprising a plurality of electrodes 21 a-d and 22 a-drespectively. The electrode assemblies 21, 22 are implanted in thediaphragm muscle so that one or more of electrodes 21 a-d and ofelectrodes 22 a-d are approximately adjacent to one or more junctions ofthe phrenic nerves 15, 16, respectively, with the diaphragm 18 muscle.Alternatively or additionally, electrodes or electrode assemblies may beimplanted on the diaphragm from the thoracic side, at a location alongthe phrenic nerve in the thoracic region, neck region or other locationadjacent a phrenic nerve (e.g. transvenously) where stimulating thephrenic nerve affects breathing and/or diaphragm movement of thesubject. In addition, leads may be subcutaneously placed to stimulate atleast a portion of the diaphragm or phrenic nerve. The electrodeassemblies 21, 22, 31, 32, 41, 42 described herein are coupled tooutputs of a pulse generator and are configured to deliver electricallystimulating signals to tissue associated with the implanted electrodeassemblies.

The electrode assemblies 21, 22 (31, 32, 41, 42) may sense as well aspace or electrically stimulate at the diaphragm muscle or at the phrenicnerve. Electrode assemblies 21, 22 may be implanted laparoscopicallythrough the abdomen and into the muscle of the diaphragm 18 withneedles, tissue expanding tubes, cannulas or other similar devices. Theelectrode assemblies 21, 22 may be anchored with sutures, staples, orother anchoring mechanisms. The electrode assemblies 21, 22 may besurface electrodes or alternatively intramuscular electrodes. The leads23, 24 coupling the electrode assemblies 21, 22 to the control unit 100are routed subcutaneously to the side of the abdomen where asubcutaneous pocket is created for the control unit 100. The electrodeassemblies 21, 22 are each flexible members with electrodes 21 a-d,assembled about 1-20 mm apart from one another and electrodes 22 a-dassembled about 1-20 mm apart from one another. The electrode assemblies21, 22 are coupled via leads 23, 24 to control unit 100. The stimulator20 further comprises one or more sensors configured to sense one or morephysiologic parameters. For example one or more sensors such as anaccelerometer or movement sensor may sense information regardingmovement pattern of the diaphragm muscles, intercostal muscles, and ribmovement and thus determine overall respiratory activity and patterns.An electrode or electrodes may be used to sense the EMG of the diaphragmto determine respiration parameters. A flow sensor may be implanted inor near the trachea to sense tracheal air flow. These sensors may beincorporated with electrode leads 21, 22, 31, 32, 41, 42 or may beseparately implanted or otherwise coupled to the subject.

The control unit 100 is configured to receive and process signalscorresponding to sensed physiological parameters, e.g., flow, nerveactivity, diaphragm or intercostal muscle movement, and/or EMG of thediaphragm 18, to determine the respiratory parameters of the diaphragm18. An EMG signal may be used or other sensed activity may alsocorrespond with either tidal volume or airflow and may be used toidentify different portions of a respiration cycle. An example of suchsignal processing or analysis is described in more detail herein withreference to a sensed respiration correlated signal, such as an EMG,flow or tidal volume correlated signal, in FIGS. 16A-16D.

The electrodes assemblies 21, 22 are coupled via leads 23, 24 toinput/output terminals 101, 102 of a control unit 100. The leads 23, 24comprise a plurality of electrical connectors and corresponding leadwires, each coupled individually to one of the electrodes 21 a-d, 22a-d. Alternatively or in addition, electrodes 31, 32 implanted on ornear the phrenic nerve in the thoracic region or electrodes 41, 42implanted on or near the phrenic nerve in the neck region. Otherlocations at or near the phrenic nerve may be stimulated as well.Electrodes may be placed at or near the hypoglossal nerve in accordancewith a variation of the invention where stimulation of the diaphragm iscoordinated with activation of upper airway muscles to open the airwaypassage just prior to stimulating the diaphragm muscles.

The control unit 100 is implanted subcutaneously within the patient, forexample in the chest region on top of the pectoral muscle. The controlunit may be implanted in other locations within the body as well. Thecontrol unit 100 is configured to receive sensed nerve electricalactivity from the electrode assemblies 21, 22, (31, 32, 41, 42)corresponding to respiratory effort or other respiration relatedparameters of a patient. The control unit 100 is also configured toreceive information corresponding to other physiological parameters assensed by other sensors. The control unit 100 delivers stimulation tothe nerves 15, 16 or diaphragm as desired in accordance with theinvention. The control unit 100 may determine when to stimulate as wellas specific stimulation parameters based on sensed information.

Additional sensors may comprise movement detectors 25, 26, in thisexample, strain gauges or piezo-electric sensors included with theelectrode assemblies 21, 22 respectively and electrically connectedthrough leads 23, 24 to the control unit 100. The movement detectors 25,26 detect movement of the diaphragm 18 and thus the respirationparameters. The movement detectors 25, 26 sense mechanical movement anddeliver a corresponding electrical signal to the control unit 100 wherethe information is processed by the processor 105. The movementinformation correlates to airflow and may accordingly be used todetermine related respiration parameters.

Electrodes may be selected from the plurality of electrodes 21 a-d and22 a-d once implanted, to optimize the stimulation response. Electrodesmay also be selected to form bipolar pairs or multipolar groups tooptimize stimulation response. Alternatively electrodes may be in amonopolar configuration. Testing the response may be done by selectingat least one electrode from the electrodes in an assembly or any othercombination of electrodes to form at least one closed loop system, byselecting sequence of firing of electrode groups and by selectingstimulation parameters. The electrodes may be selected by an algorithmprogrammed into the processor that determines the best location andsequence for stimulation and/or sensing nerve and/or EMG signals, e.g.,by testing the response of the electrodes by sensing respiratory effortor flow in response to stimulation pulses. Alternatively, the selectionprocess may occur using an external programmer that telemetricallycommunicates with the processor and instructs the processor to causestimulation pulses to be delivered and the responses to be measured.From the measured responses, the external programmer may determine theoptimal electrode configuration, by selecting the electrodes to have anoptimal response to delivery of stimulation.

Alternative mapping techniques may be used to place one or morestimulation electrodes on the diaphragm. Examples of mapping thediaphragm and/or selecting desired locations or parameters for desiredstimulation responses are described for example in U.S. application Ser.No. 10/966,484 filed Oct. 15, 2004 and entitled: SYSTEM AND METHOD FORMAPPING DIAPHRAGM ELECTRODE SITES; in U.S. application Ser. No.10/966,474, filed Oct. 15, 2004 entitled: BREATHING THERAPY DEVICE ANDMETHOD; in U.S. application Ser. No. 10/966,472 filed Oct. 15, 2004entitled: SYSTEM AND METHOD FOR DIAPHRAGM STIMULATION; U.S. applicationSer. No. 10/966,421 filed Oct. 15, 2004 entitled: BREATHING DISORDER ANDPRECURSOR PREDICTOR AND THERAPY DELIVERY DEVICE AND METHOD; and in U.S.application Ser. No. 10/686,891 filed Oct. 15, 2003 entitled BREATHINGDISORDER DETECTION AND THERAPY DELIVERY DEVICE AND METHOD, all of whichare fully incorporated herein by reference.

FIG. 2 illustrates an implantable control unit 100. The control unit 100includes electronic circuitry capable of generating and/or deliveringelectrical stimulation pulses to the electrodes or electrode assemblies21, 22, 31, 32, 41, 42, through leads 23, 24, 33, 34, 43, 44,respectively, to cause a diaphragm respiratory response in the patient.For purposes of illustration, in FIG. 2, the control unit 100 is showncoupled through leads 23, 24 to electrode assemblies 21, 22respectively. Other leads as described herein may be connected to inputs101, 102.

The control unit 100 comprises a processor 105 for controlling theoperations of the control unit 100. The processor 105 and otherelectrical components of the control unit are coordinated by an internalclock 110 and a power source 111 such as, for example a battery sourceor an inductive coupling component configured to receive power from aninductively coupled external power source. The processor 105 is coupledto a telemetry circuit 106 that includes a telemetry coil 107, areceiver circuit 108 for receiving and processing a telemetry signalthat is converted to a digital signal and communicated to the processor105, and a transmitter circuit 109 for processing and delivering asignal from the processor 105 to the telemetry coil 107. The telemetrycoil 107 is an RF coil or alternatively may be a magnetic coil. Thetelemetry circuit 106 is configured to receive externally transmittedsignals, e.g., containing programming or other instructions orinformation, programmed stimulation rates and pulse widths, electrodeconfigurations, and other device performance details. The telemetrycircuit is also configured to transmit telemetry signals that maycontain, e.g., modulated sensed and/or accumulated data such as sensedEMG activity, sensed flow or tidal volume correlated activity, sensednerve activity, sensed responses to stimulation, sensed positioninformation, sensed movement information and episode counts orrecordings.

The leads 23, 24 are coupled to inputs 101, 102 respectively, of thecontrol unit 100, with each lead 23, 24 comprising a plurality ofelectrical conductors each corresponding to one of the electrodes orsensors (e.g., movement sensor) of the electrode assemblies 23, 24. Thusthe inputs 101, 102 comprise a plurality of inputs, each inputcorresponding to one of the electrodes or sensors. The signals sensed bythe electrode assemblies 21, 22 are input into the control unit 100through the inputs 101, 102. Each of the inputs are coupled to aseparate input of a signal processing circuit 116 (schematicallyillustrated in FIG. 2 as one input) where the signals are thenamplified, filtered, and further processed, and where processed data isconverted into a digital signal and input into the processor 105. Eachsignal from each input is separately processed in the signal processingcircuit 116.

The EMG/Phrenic nerve sensing has a dual channel sensor. Onecorresponding to each lung/diaphragm side. However, sensing can beaccomplished using a single channel as the brain sends signals to theright and left diaphragm simultaneously. Alternatively, the EMG orphrenic nerve collective may be sensed using a single channel. Either adual channel or single channel setting may be used and programmed.

The control unit 100 further includes a ROM memory 118 coupled to theprocessor 105 by way of a data bus. The ROM memory 118 provides programinstructions to the control unit 100 that direct the operation of thestimulator 20. The control unit 100 further comprises a first RAM memory119 coupled via a data bus to the processor 105. The first RAM memory119 may be programmed to provide certain stimulation parameters such aspulse or burst morphology; frequency, pulse width, pulse amplitude,duration and a threshold or trigger to determine when to stimulate. Asecond RAM memory 120 (event memory) is provided to store sensed datasensed, e.g., by the electrodes of one or more electrode assemblies 21,22(EMG or nerve activity), position sensor 121, diaphragm movementsensors or strain gauges 25, 26, or the accelerometer 122 or othersensors such as a flow or tidal volume correlated sensors (e.g. usingmovement sensors or impedance plethysmography with a sensor positionedat one or more locations in the body such as on the control unit 100.These signals may be processed and used by the control unit 100 asprogrammed to determine if and when to stimulate or provide otherfeedback to the patient or clinician. Also stored in RAM memory 120 maybe the sensed waveforms for a given interval, and a count of the numberof events or episodes over a given time as counted by the processor 105.The system's memory will be programmable to store informationcorresponding to breathing parameters or events, stimulation deliveredand responses, patient compliance, treatment or other relatedinformation. These signals and information may also be compiled in thememory and downloaded telemetrically to an external device 140 whenprompted by the external device 140.

An example of the circuits of the signal processing circuit 116corresponding to one or more of the sensor inputs is illustratedschematically in FIG. 16A. A sensor input signal correlating orcorresponding to EMG, tidal volume or flow is input into an amplifier130 that amplifies the signal. The signal is then filtered to removenoise by filter 131. The amplified signal is rectified by a rectifier132, is converted by an A/D converter 133 and then is integrated byintegrator 134 to result in an integrated signal from which respiratoryinformation can be ascertained. A flow correlated signal may be inputthrough A/D converter 133 a and then input through the integrator 134.The signal output of the integrator 134 is then coupled to the processor105 and provides a digital signal corresponding to the integratedwaveform to the processor 105. A tidal volume correlated signal may alsobe input to the signal processing circuit through A/D converter 134 a atthe output of the integrator 134. The signal output of the integrator134 is coupled to a peak detector 135 that determines when theinspiration period of a respiratory cycle has ended and an expirationcycle has begun. The signal output of the integrator 134 is furthercoupled to a plurality of comparators 136, 137. The first comparator 136determines when respiration has been detected based on when anintegrated signal waveform amplitude has been detected that is greaterthan a percentage value of the peak of an intrinsic respiratory cycle oranother predetermined amount (comp 1), for example between 1-25% of theintrinsic signal. In this example, the comparator is set at a value thatis 10% of the waveform of an intrinsic respiratory cycle. The secondcomparator 137 determines a value of the waveform amplitude (comp 2)when an integrated signal waveform amplitude has been detected that isat a predetermined percentage value of the peak of an intrinsicrespiratory cycle or another predetermined amount, for example between75%-100% of the intrinsic signal. In this example, the comparator is setat a value that is 90% of the waveform of an intrinsic respiratorycycle. From this value and the comp 1 value, the slope of theinspiration period (between 10% and 90% in this example) may bedetermined. This slope may provide valuable diagnostic information as itshows how quickly a patient inhales.

In the case of a signal correlating to flow that is integrated or asignal correlated to tidal volume, after (or when) the peak detectordetects the end of an inhalation period and the beginning of anexhalation period, the third comparator 138 determines an upper valuefor the waveform amplitude during active exhalation period, for examplebetween 100% and 75% of the peak value detected by the peak detector135. Then a lower value (comp 4) of the waveform during the exhalationperiod is determined by the fourth comparator 139, which compares themeasured amplitude to a predetermined value, e.g. a percentage value ofthe peak amplitude. In this example, the value is selected to be 10% ofthe peak value. In one embodiment this value is selected to roughlycoincide with the end of a fast exhalation period. From comp 3 and comp4 values, the slope of the exhalation period (between 10% and 90% inthis example) may be determined. This slope may provide valuablediagnostic information as it shows how quickly a patient exhales.

A non-integrated flow signal may also be used, for example inconjunction with EMG to detect airway closure where EMG is present inthe absence of flow.

FIG. 16B illustrates two sequential integrated waveforms of exemplaryintegrated signals corresponding to two serial respiratory cycles. Aninspiration portion 172 may be observed using an EMG, flow or tidalvolume correlated signal. An exhalation period 176 may be observed usinga flow or tidal volume correlated signal. The waveform 170 has abaseline 170 b, inspiration cycle 171, a measured inspiration cycle 172,a point of 10% of peak inspiration 173 (comp 1), a point of 90% of peakof inspiration 174 (comp 2), a peak 175 where inspiration ends andexhalation begins, and exhalation cycle 176 a fast exhalation portion177 of the exhalation cycle 176, a 90% of peak exhalation point 178(comp 3), a 10% of peak exhalation point 179 (comp 4), an actualrespiratory cycle 180 and a measured respiratory cycle 181. The secondwaveform 182 is similarly shaped. The 10% inspiration 183 of the secondwaveform 182 marks the end of the measured respiratory cycle 181, whilethe 10% point 173 of the waveform 170 marks the beginning of themeasured respiratory cycle 181.

FIG. 16C illustrates a schematic EMG envelope corresponding to aninspiration portion e.g., 172 of a respiration cycle. FIG. 16Dillustrates a schematic flow correlated signal corresponding to arespiration cycle.

In FIG. 3 a circuit for an external device 140 is illustrated. Theexternal device 140 comprises a processor 145 for controlling theoperations of the external device. The processor 145 and otherelectrical components of the external device 140 are coordinated by aninternal clock 150 and a power source 151. The processor 145 is coupledto a telemetry circuit 146 that includes a telemetry coil 147, areceiver circuit 148 for receiving and processing a telemetry signalthat is converted to a digital signal and communicated to the processor145, and a transmitter circuit 149 for processing and delivering asignal from the processor 145 to the telemetry coil 146. The telemetrycoil 147 is an RF coil or alternatively may be a magnetic coil dependingon what type of coil the telemetry coil 107 of the implanted controlunit 100 is. The telemetry circuit 146 is configured to transmit signalsto the implanted control unit 100 containing, e.g., programming or otherinstructions or information, programmed stimulation protocols, rates andpulse widths, electrode configurations, and other device performancedetails. The telemetry circuit 146 is also configured to receivetelemetry signals from the control unit 100 that may contain, e.g.,sensed and/or accumulated data such as sensed information correspondingto physiological parameters, (e.g., sensed EMG activity, sensed nerveactivity, sensed responses to stimulation, sensed position information,sensed flow, or sensed movement information). The sensed physiologicalinformation may be stored in RAM event memory 158 or may be uploaded andthrough an external port 153 to a computer, or processor, eitherdirectly or through a phone line or other communication device that maybe coupled to the processor 145 through the external port 153. Theexternal device 140 also includes ROM memory 157 for storing andproviding operating instructions to the external device 140 andprocessor 145. The external device also includes RAM event memory 158for storing uploaded event information such as sensed information anddata from the control unit, and RAM program memory 159 for systemoperations and future upgrades. The external device also includes abuffer 154 coupled to or that can be coupled through a port to auser-operated device 155 such as a keypad input or other operationdevices. Finally, the external device 140 includes a display device 156(or a port where such device can be connected), e.g., for displayvisual, audible or tactile information, alarms or pages.

The external device 140 may take or operate in, one of several forms,e.g. for patient use, compliance or monitoring; and for health careprovider use, monitoring, diagnostic or treatment modification purposes.The information may be downloaded and analyzed by a patient home unitdevice such as a wearable unit like a pager, wristwatch or palm sizedcomputer. The downloaded information may present lifestyle modification,or compliance feedback. It may also alert the patient when the healthcare provider should be contacted, for example if there ismalfunctioning of the device or worsening of the patient's condition.

Other devices and methods for communicating information and/or poweringstimulation electrodes as are know in the art may be used as well, forexample a transcutaneously inductively coupled device may be used topower an implanted device.

According to one aspect of the invention, the stimulator operates tostimulate and/or manipulate breathing to mitigate (i.e., avoid or reduceeffects of) an obstructive respiratory event by stimulating the phrenicnerve, diaphragm or associated tissue according to one or moreprotocols, to elicit a respiratory response. Examples of suchstimulation protocols are described herein with reference to FIGS.4A-16D. In accordance with another aspect of the invention, suchstimulation is provided prior to the onset of an obstructive respiratoryevent or prior to airway obstruction to prevent an obstructiverespiratory event from occurring or the airway from fully closing. Inaccordance with another aspect of the invention, stimulation is providedat a low level following obstructive sleep apnea or effective airwayclosure.

In accordance with one aspect of the invention as described with respectto FIGS. 4A-4D, 5A-5C, 7A-7B, 8A-8B, 9A-9C, 10A-10C and 12A-12B,stimulation of the phrenic nerve or diaphragm is provided to increasefunctional residual capacity, i.e., end expiratory volume, at leastuntil onset of a subsequent respiration cycle. In accordance with theinvention, an increased functional residual capacity is believed toassist in maintaining an airway passage open to a sufficient degree toprevent or reduce airway collapse that results in an obstructiverespiratory event.

In accordance with another aspect of the invention, as described withrespect to FIGS. 4A-4D, 5A-5B, 6A-6B, 10A-10C, 11A-11B, 12A-12B or14A-14B, stimulation of the phrenic nerve or diaphragm is provided toincrease tidal volume sufficiently to increase upper airway patency. Itis believed that increasing the tidal volume may contribute tostiffening the upper airway. Preferrably the same or a lower peak flowwith respect to intrinsic flow is provided to avoid an increase innegative pressure applied to the upper airway that would decrease upperairway patency. Therapy may be delivered to increase flow in the casewhere flow is below normal. In cases where flow is normal, or limited byobstruction, tidal volume may be increased through extension of theinspiration duration. An upper airway hysteresis effect may also occurwhere the volume of a breath is increased above a normal tidal volumeand the stiffening of the upper airway during inspiration does notreturn entirely to a relaxed resting state. It is accordinglyadditionally believed that an upper airway hysteresis effect wouldstiffen the upper air passageway for subsequent breaths and will therebyprevent or mitigate airway narrowing or collapse that results inobstructive sleep apnea.

In accordance with one aspect of the invention, as described withrespect to FIGS. 9A-9C, 11A-11B, 13A-13B and 14A-14B, stimulation isprovided to create ventilatory stability and to thereby reducefluctuations in the upper airway passage muscles that may lead to upperairway collapse where ventilatory drive is low or unstable. “Ventilatoryinstability is defined herein to mean varying breathing rate and/ortidal volume outside of normal variations.” Ventilatory stabilityassociated with obstructive respiratory events, as opposed to periodicbreathing or Cheynes-Stokes respiration, include, for example,variations in breathing rate and/or tidal volume associated with sleeponset, change in sleep state, and REM sleep.

In accordance with another aspect of the invention, as described withrespect to FIGS. 4A-4D, 6A-6C, 9A-9C and 10A-10C, 11A-11B, 12A-12B, and14A-14B, stimulation of the phrenic nerve or diaphragm is providedduring intrinsic breathing during or at the end of an intrinsicinspiration portion of a breathing cycle. For purposes of the inventionherein, the intrinsic cycle may be detected near onset of inspiration.Other portions of a breathing cycle may be identified for breathingstimulation. Alternatively, the beginning of the breathing cycle or aportion of the breathing cycle may be predicted, e.g., based on atypical breathing pattern of an individual patient.

A stimulation signal may be provided during inspiration of intrinsicbreathing for various purposes. In accordance with a variation of theinvention, stimulation is provided during intrinsic inspiration toprovide initial and more gradual control of breathing according to aprotocol. Then, breathing control protocols may be applied so thatairway closure due to stimulation is avoided. Tidal volume is increasedgradually so as to balance out an increase in upper airway resistancethat can occur with stimulation during intrinsic inspiration.Stimulation of breathing during intrinsic inspiration in accordance withvariations of the invention is configured to contribute to creating theeffect of increasing functional residual capacity. In some variations ofthe invention, stimulation during intrinsic breathing is configured tostiffen the upper airway, thereby increasing upper airway patency.Stimulating during inspiration in accordance with a protocol of theinvention may also increase upper airway hysteresis. In one embodiment,breathing is stimulated at least in part during intrinsic inspiration sothat the resulting tidal volume is greater than intrinsic normal volume,while peak flow is maintained near normal peak flow to avoid upperairway closure. Stimulating during intrinsic inspiration may also beused to normalize breathing in an obstructive sleep apnea patient and toincrease ventilatory stability associated with airway obstructions.Stimulating at least in part during intrinsic inspiration may increaseinspiration duration which may allow increase of tidal volume withoutsignificantly increasing the peak flow. (Increasing peak flow mayincrease the possibility of airway closure.) According to oneembodiment, peak flow is provided at, near or below intrinsic peak flow.

While stimulating breathing during intrinsic inspiration is describedherein in use with a device and method of treating obstructive sleepapnea, other breathing or related disorders may be treated bystimulating breathing during intrinsic inspiration in accordance withanother aspect of the invention.

In accordance with another aspect of the invention and as illustrated inFIGS. 4A-4D, and 5A-5C the phrenic nerve or diaphragm is stimulated toprovide deep inspiration therapy to a subject. Deep inspiration therapyinvolves stimulating a breath that is of a greater tidal volume than anormal breath. According to a preferred embodiment, deep inspirationstimulation provides a breath having a greater inspiration duration thanthat of a normal breath. Rather than substantially increasing peak flowor rather than increasing the magnitude of diaphragm contraction, theincrease in inspiration duration to increase tidal volume is believed toreduce the likelihood of airway closure with stimulation. Deepinspiration stimulation may be provided intermittently throughout thenight or a portion of the night while a patient sleeps, thus preventingan obstructive respiratory event. While deep inspiration therapy isdescribed herein in use with a device and method of treating obstructivesleep apnea, other breathing or related disorders may be treated by deepinspiration therapy.

In accordance with another aspect of the invention as described withrespect to FIGS. 6A-6B, 7A-7B, 8A-8B, 9A-9C, 10A-10C and 12A-12B, theexhalation cycle is manipulated to provide a therapeutic effect.According to one aspect of the invention, increased functional residualcapacity is provided by manipulating the exhalation phase. Manipulationof the exhalation phase may be provided using stimulation during theexhalation phase. The exhalation phase may also otherwise be manipulatedin length or duration.

In accordance with another aspect of the invention as described withrespect to FIGS. 7A-7B 8A-8B, 9A-9C, and 10A-10C, a low levelstimulation is applied during all or a portion of the respiration cycle.Among other therapeutic effects such stimulation may increase functionalresidual capacity. Such low level stimulation may be directed to providean increased tidal volume during a rest phase of a respiration cycle bysustaining a low level contraction of the diaphragm. Typically such lowlevel stimulation would be lower than the relative threshold foreliciting breathing. This level may vary from patient to patient and maybe determined on an individual basis. It may also depend on electrodetype and placement. Typically the stimulation is lower than 8 mA.

In accordance with another aspect of the invention, as described withrespect to FIGS. 9A-9C, 12A-12B, 13A-13B, and 14A-14B, stimulation ofthe phrenic nerve or diaphragm is provided to control breathing.According to one aspect of the invention, breathing is controlled eitherby inhibiting respiratory drive, entraining breathing or othermechanisms. Controlling breathing according to one variation comprisesstimulating to control or manipulate the central respiratory drive.Controlling breathing may include taking over breathing to control oneor more parameters of a stimulated breath. Entraining breathing mayinclude stimulating at a rate greater than but close to, or equal to theintrinsic respiratory rate until the central pattern generator activatesthe respiration mechanisms, which includes those of the upper airway, inphase with the stimulation. As an alternative or in addition,inspiration duration may be increased with respect to the totalrespiration cycle or exhalation. While controlling breathing isdescribed herein in use with a device and method of treating obstructivesleep apnea, other breathing or related disorders may be treated bycontrolling breathing in accordance with another aspect of theinvention.

According to another aspect of the invention stimulation is used toprovide ventilatory stability. Examples of providing ventilatorystability are shown in FIGS. 9A-9C, 10A-10B, 11A-11B, 13A-13B and14A-14B. Ventilatory stability may be provided by stimulating breathingto increase a falling tidal volume towards that of a normal breath.Ventilatory stability may also be provided by controlling breathing in amanner that creates stability. Ventilatory stability may also beprovided by entraining breathing. Instability in ventilatory rate thatindicates the onset of obstructive sleep apnea may be treated bycontrolling breathing for a preset period of time as described withrespect to FIGS. 9A-9B, 13A-13B or FIGS. 14A-14B. Instability inventilatory rate may also be treated by normalizing tidal volume usingstimulation as described with respect to FIGS. 10A-10B or 11A-11B.

Referring to FIGS. 4A-4D, stimulation and respiration waveformsillustrating a method using a device in accordance with one aspect ofthe invention are illustrated. A device and method creates increasedfunctional residual capacity and upper airway patency by providing deepinspiration. In this particular embodiment, deep inspiration is providedby stimulating during a portion of an inspiration cycle. Stimulation mayextend beyond the duration of an intrinsic breath. The stimulation isprovided to increase tidal volume by extending the duration of theinspiration cycle. (While preferably maintaining peak flow at or nearintrinsic peak flow, i.e. normalizing flow.) In accordance with aprotocol, stimulation through one or more electrodes associated with thediaphragm or phrenic nerve is provided to cause the diaphragm tocontract to cause a deep inspiration breath. Stimulation may be providedwhen a characteristic preceding an obstructive respiratory event isdetected. For example, if erratic breathing occurs or if the tidalvolume drops below a given threshold level, then stimulation isprovided. The resulting breath comprises a deep inhalation breath (i.e.,a greater tidal volume than a normal, intrinsic breath.) A deepinspiration breath may then be repeated periodically to prevent furtherdrop in tidal volume by increasing the functional residual capacity andcreating upper airway stiffening. The device may also be programmed torepeat the deep breath a given number of times before ceasing thestimulation.

One possible characteristic of breathing in obstructive sleep apneapatients is a decreasing tidal volume. The ultimate closure of an airpassageway in an obstructive sleep apnea event thus may be preceded by agradual decrease in ventilatory volume. Another possible characteristicof breathing in obstructive sleep apnea patients is an erratic breathingpattern. In a patient who is diagnosed with obstructive sleep apnea,respiration may be monitored using EMG or other sensors that senserespiration parameters corresponding to tidal volume or flow (forexample, diaphragm movement which corresponds to airflow may be sensed;impedance plethysmography may be used; or flow itself may be sensedusing a sensor implanted in the trachea.) FIGS. 16A-16D illustratemonitoring or detection of various aspects or parameters of respirationon a breath by breath basis. Tidal volume is monitored and a decrease intidal volume characteristic (FIG. 4A) or an erratic breathing pattern(FIG. 4B) in an obstructive sleep apnea patient is detected. (Monitoredtidal volume as used herein may also include a monitored tidal volumecorrelated signal). Estimated minute ventilation (i.e., determined bymultiplying respiratory rate times volume of a breath) may also be usedto determine the impending onset of an obstructive respiratory event.

For purposes of detecting a threshold volume on a breath-by-breath basisor in real time, a programmed threshold may be set. The threshold valuemay be determined when initializing the device as the value at or belowwhich preventative or mitigating treatment is required or is otherwiseoptimal. This value may be programmed into the device. A minimum safetythreshold value may also be established below which stimulation isinhibited to prevent airway closure. As such, the minimum safetythreshold may be set as a value sufficiently above a tidal volume wherestimulation treatment if provided would further close an air passageway.

When monitoring tidal volume, the area under the inspiration flow curveor EMG envelope of an individual breath may be monitored to determinetidal volume of a breath. The tidal volume is compared to a thresholdvalue for a particular patient. Other parameters may be used to identifywhen tidal volume has dropped below a predetermined threshold, forexample baseline tidal volume rate variance over a period of time may bemonitored and compared to a normal variance. The normal variance may bedetermined on a patient-by-patient basis and programmed into the device.

FIG. 4A illustrates a breathing pattern where a decrease in tidal volumeultimately ends in an obstructive sleep apnea event. Accordingly, tidalvolume of intrinsic breaths 411-415 of an obstructive sleep apneapatient is shown in FIG. 4A. The tidal volume of breaths 411-415gradually decreases until the airway narrows ultimately leading to anairway obstruction. An obstructive respiratory event occurs with totalairway closure after breath 415. An obstructive respiratory event mayalso be an airway narrowing, e.g., hypopnea. An obstructive respiratoryevent may be detected by monitoring a decrease in tidal volume, forexample as a predetermined percentage of normal or intrinsic tidalvolume. The threshold 450 below which treatment is to be provided by thedevice is shown in FIGS. 4A-4D. FIG. 4D illustrates a stimulationprotocol corresponding to the resulting tidal volume waveforms of FIG.4C.

FIG. 4C illustrates tidal volume of a patient treated using a deepinspiration stimulator. The stimulator detects the drop in tidal volume(breath 413) below a threshold level as described above with respect toFIGS. 4A-4B. During the subsequent breath 414, stimulation 434(schematically illustrated as an envelope of a burst of pulses) isprovided by the stimulator to provide a deep inspiration breath 424 withthe breath 414. The deep inspiration breath 424 comprises a breath thathas a tidal volume greater than the tidal volume of a normal orintrinsic breath. After one or more deep inspiration breathstimulations, the tidal volume is expected to return to normal or closeto normal, e.g. at breaths 425-429. Synchronization is provided wherebythe onset of inspiration is detected and stimulation is provided duringthe breath. According to one variation, a tidal volume that is greaterthan or equal to a predetermined percentage of a normal inspiration isdetected(e.g. 10% of tidal volume as described with respect to FIGS.16A-16D). Then when the onset of the next inspiration is detected,stimulation is provided. Additional periodic delivery of deepinspiration paced breaths may be provided synchronously orasynchronously with the intrinsic breathing, to prevent or mitigatedrops in tidal volume. In accordance with this aspect of the invention,as illustrated in FIG. 4D an additional pacing pulse or burst of pulses439 is provided to stimulate deep inspiration breath 419. Thus, thetherapy described with reference to FIG. 4D may prevent a further dropin tidal volume, thereby reducing the occurrence of obstructiverespiratory events or other breathing related disorders.

FIGS. 5A-5C illustrate use of a deep inspiration stimulator inaccordance with the invention. FIG. 5A illustrates a breathing patternwhere a decrease in tidal volume ultimately ends in an obstructiverespiratory event. Accordingly, tidal volume of intrinsic breaths511-515 of an obstructive sleep apnea patient is shown in FIG. 5A withthe airway ultimately closing after breath 515. In FIG. 5A, no treatmentis provided. Other pre-obstructive breathing characteristics may also beused to determine when an OSA event is likely to be imminent.

A threshold 550 below which treatment is to be provided by the device isshown in FIGS. 5A and 5B. This threshold may be determined in a mannersimilar to that described with respect to FIGS. 4A-4C. FIG. 5Cillustrates a stimulation protocol corresponding to the resulting tidalvolume waveforms of FIG. 5B. FIG. 5B illustrates the tidal volume of apatient treated using a deep inspiration stimulator who would otherwisehave had a breathing pattern shown in FIG. 5A. The stimulator detectsthe drop in tidal volume (breath 513) below a threshold level 550 in amanner similar to that described above with respect to FIGS. 4A-4D.Prior to what would have been the subsequent breath 514, i.e., at somepoint during the intrinsic exhalation period or rest period, thestimulator provides stimulation 533 to elicit a deep inspiration breath523 (FIG. 5B). The deep inspiration breath 523 comprises a breath with atidal volume greater than the tidal volume of an intrinsic or normalbreath. Preferrably, the peak flow remains relatively normal whileinspiration duration increases thus increasing tidal volume. After oneor more deep inspiration breath stimulations, the tidal volume returnsto normal, e.g., at breaths 524-525. At breaths 526, 527 a slightdecrease in respiratory drive is shown with a decreased tidal volume.Periodic delivery of deep inspiration breaths may be provided to preventor mitigate drops in tidal volume. In accordance with this aspect of theinvention, as illustrated in FIG. 5C an additional pacing pulse or burstof pulses 538 is provided prior to the onset of the next intrinsicbreath to stimulate deep inspiration breath 528 which is then followedby a normal breath 529. The deep inspiration breaths 523 or 528 areintended to increase the functional residual capacity of the lung and/orenhance upper airway patency. Thus, the therapy may prevent further dropin tidal volume, thereby reducing the incidence of obstructive sleepapnea or other breathing related disorders.

FIGS. 6A-6B illustrate stimulation and inspiration waveformscorresponding to a variation of stimulation device and method of theinvention. The stimulation protocol of FIGS. 6A-6B provides stimulationat the end of an inspiration cycle increasing inspiration duration,thereby increasing tidal volume. A resulting normalized peak flow andincreased tidal volume is believed to stiffen or lengthen the upperairway and may create an upper airway hysteresis effect Increased tidalvolume may provide more time and volume for gas exchange. Among othereffects, normalized peak flow and increased tidal volume are believed toprevent airway collapse attributable to obstructive sleep apnea.

FIG. 6A illustrates normal inspiration duration 610 of an intrinsicbreath and increased inspiration duration 620 that would result fromstimulation 650 shown in FIG. 6B. Stimulation 650 is provided at the endof an inspiration period for a predetermined amount of time T₆ tomaintain flow and prolong inspiration for the additional period of timeT₆. The end of the inspiration period may be determined in a manner asdescribed with reference to FIGS. 16A-16D herein. The time T₆ may beselected and/or programmed into the device. The time may be determinedto elicit a desired response. A short stimulation period, for example,as short as 0.1 seconds may be used.

FIGS. 7A-7B illustrate stimulation and inspiration waveformscorresponding to a variation of a stimulation device and method of theinvention. The stimulation protocol of FIGS. 7A-7B provides low levelstimulation at the beginning or the end of an exhalation portion of arespiration cycle, or at some time within the exhalation portion of therespiration cycle. This is believed to preserve lung volume prior to thenext inspiration. The manipulation of the exhalation cycle is thusbelieved to increase functional residual capacity. FIG. 7A illustratestidal volume 730 that would result from stimulation 750 shown in FIG.7B. Stimulation 750 is provided at an end portion of an exhalation cycleto preserve some volume 740 for the next inspiration cycle thusincreasing the functional residual capacity. The end of the exhalationcycle may be determined by determining the end of inspiration and thenbased on a known respiration rate, estimating the time of the end of theexhalation cycle. Alternatively, flow correlated respiration parametersmay be sensed and the desired portion of the exhalation cycle may bedetermined. FIGS. 16A-16D illustrate manners for determining portions ofa respiration cycle.

FIGS. 8A-8B illustrate stimulation and inspiration waveformscorresponding to a variation of a stimulation device and method or theinvention. The stimulation protocol of FIG. 8B provides a low level of acontinuous stimulation to cause the diaphragm to remain slightlycontracted, thereby increasing functional residual capacity. FIG. 8Billustrates stimulation provided while FIG. 8A illustrates tidal volume.As shown, the tidal volume is elevated during the end portion of theexhalation cycle 840 (FIG. 8A) relative to end expiratory tidal volumebefore the stimulation.

FIGS. 9A-9C illustrate stimulation and inspiration waveformscorresponding to a variation of a stimulation device and method of theinvention. The stimulation protocol provides a combination of therapiesor protocols including increasing functional residual capacity andcontrolling breathing. The stimulation protocols manipulate exhalationand control breathing. The stimulation protocol of FIGS. 9A-9C providesa low current stimulation 950 as shown in FIG. 9C during the exhalationphase of a respiration cycle and a stimulated breath 951 delivered atthe end of exhalation. The stimulated breath 951 is provided at a higherrate R2 than the intrinsic rate R1. The stimulation 950 is appliedbetween the end of inspiration cycles 920, 921, 922 and the onset of thenext inspiration cycles, 921, 922, 923 respectively to increasefunctional residual capacity. Stimulation 951 produces inspirationcycles 920, 921, 922, 923. Flow waveforms 930, 931, 932, 933respectively of respiration cycles 920, 921, 922, 923 are shown in FIG.9A. Tidal volume waveforms 940, 941, 942, 943 respectively ofrespiration cycles 920, 921, 922, 923 are shown in FIG. 9B.

FIGS. 10A-10B illustrate stimulation and inspiration waveformscorresponding to a variation of a stimulation device and method of theinvention. Stimulation is provided during the inspiration cycle in amanner shown in FIGS. 7A-7B to increase inspiration duration and tidalvolume (with normalized peak flow) in order to stiffen the upper airway.Also, a low level stimulation is provided to increase lung capacity atthe end of inspiration and until the beginning of the next inspirationcycle to increase the functional residual capacity. A first intrinsicrespiration cycle 1020 is illustrated. At the onset of exhalation 1021of the respiration cycle 1020, a low level stimulation 1050 is applieduntil the onset of the inspiration cycle of the next respiration cycle1022. At the detection of the onset of the next respiration cycle 1022(as described in FIGS. 16A-16D), stimulation 1055 is provided. Thestimulation 1055 is applied at least in part during the inspirationcycle 1022. The corresponding tidal volumes 1040, 1042 of respirationcycles 1020, 1022 respectively are illustrated in FIG. 10A. Thecorresponding flows 1030, 1032 of respiration cycles 1020, 1022respectively are shown in FIG. 10B.

Referring to FIGS. 11A and 11B, stimulation and inspiration waveformsillustrate a stimulation device and method of the invention. Stimulationis provided in a manner similar to that described with reference toFIGS. 4A-4D. In accordance with FIGS. 11A and 11B, stimulation isprovided to prevent or mitigate obstructive sleep apnea by stabilizingthe tidal volume. FIG. 11A schematically shows the tidal volume assensed by EMG sensors and illustrates the intrinsic breathing 1111-1117of a subject, as well as the resulting breathing 1124, 1125. FIG. 11Billustrates the stimulation pulse envelopes 1160 of stimulation appliedto the diaphragm or phrenic nerve of a subject in accordance with oneaspect of the invention. Referring to FIG. 11A, the tidal volume fromintrinsic breathing gradually decreases (1111, 1112) until it fallsbelow a threshold level 1150 (1113-1115) and then resumes normal tidalvolume (1116-1117) after treatment. After breath 1113 is detected belowthreshold level 1150, a stimulation pulse 1160 is provided during and insynchronization with the subsequent breath 1114, 1115 to thereby providethe resulting breath. The resulting breaths have waveforms 1124, 1125with tidal volumes increased to a level of normal breathing. Accordingto one variation, stimulation is provided with the goal of stabilizingor normalizing breathing. After stimulating for a given period of timeor number of breaths, breathing is monitored to determine if it isnormalized (for example with breaths 1116, 1117) at which time thestimulation may be discontinued.

FIGS. 12A-12B illustrate stimulation and inspiration waveformscorresponding to a variation of a stimulation device and method of theinvention. The stimulation protocol of FIGS. 12A-12B provides a longrising stimulation during at least the inspiration portion of arespiration cycle to increase inspiration time of the cycle with respectto expiration time(or total percentage of the cycle that corresponds toinspiration). Using breathing control therapy to lengthen theinspiratory duration, expiratory time is reduced and the baselinerelaxation lung volume is not completely restored, leading to anincreased functional residual capacity. The stimulation protocol therebymanipulates or shortens the length of the exhalation portion of therespiration cycle. In addition, the respiration rate is increased toshorten the exhalation portion of the respiration waveform. Thus, theprotocol is directed to increasing the functional residual capacity ofthe lungs by manipulating the expiration phase of the respiration cycle.

FIG. 12A illustrates flow and FIG. 12B illustrates correspondingstimulation. Referring to FIG. 12A a first intrinsic breath 1210 isshown with an intrinsic inspiration volume V_(II) and an intrinsicexpiration volume V_(IE). Prior to time T_(12A), breathing may beentrained (for example, as described with respect to FIGS. 13A and 13Bherein) at a rate slightly faster than the intrinsic rate but atapproximately a normal tidal volume and waveform 1210. Thereafter,stimulation 1240 is applied during a rest period (i.e. at an end portionof the exhalation phase) of a respiration cycle 1220 following breath1210. The stimulation is provided using a long rising pacing pulse sothat the respiration cycle is lengthened by a time T_(12B) to preventfull expiration before the next inspiration cycle of the next breath1230 which is provided by stimulation 1250. Stimulation 1250 is providedat a rate slightly faster than the previous stimulation 1240. Thus,exhalation is shortened, preventing exhalation portion 1260, and thusincreasing the functional residual capacity of the lungs.

Referring to FIGS. 13A-13B, stimulation and respiration waveformsillustrating a stimulation method using a stimulation device inaccordance with one aspect of the invention are illustrated. Accordingto FIGS. 13A-13B, breathing is stabilized by stimulating to control ormanipulate breathing. FIGS. 13A-13B illustrate a variation of atechnique for controlling breathing.

FIG. 13A illustrates the flow of air representing respiration waveformsover time. Breathing control may be used for a number of differentpurposes. It may be done with or without sensing a condition thatindicates a respiratory disturbance is present or occurring. It may bedone for a predetermined period of time or during certain times of dayor during certain sleep cycles. It may be done to stabilize breathing.

For example, if tidal volume falls below a predetermined threshold,stimulation may begin. Stimulation may also be provided periodically orat times of greater vulnerability to obstructive sleep apnea or otherdisorders associated with breathing disorders. FIG. 13B illustratesenvelopes 1340 of stimulation pulses provided to control breathingduring the course of stimulation. FIG. 13A illustrates the breaths 1360resulting from the stimulation illustrated in FIG. 13B.

According to this embodiment, the stimulator first takes over breathingby providing stimulation 1340(as illustrated in FIG. 13B) at a timeduring an end portion 1320 of the exhalation phase of an intrinsicrespiration cycle, prior to the onset of the next respiration cycle (Asillustrated in FIG. 13A). The stimulation 1340 is provided at a rategreater than the intrinsic rate, i.e., where the cycle length T1 is lessthan the intrinsic cycle length T1+x. As illustrated the duration of theintrinsic respiration cycle is T₁+x. The duration of the respirationcycles of the stimulated breathing begins at T₁ to take over breathing.After a period of time of taking over breathing, the respiration cyclelength is then gradually increased to T1+m, t1+n, and T1+o where m<n<o<xand where o approaches x in value. Breathing is thereby controlled andventilation is accordingly stabilized.

According to one aspect of the invention, breathing is believed to becontrolled by stimulating for a period of time at a rate greater thanbut close to the intrinsic respiratory rate. Breathing may be controlledthrough inhibition of the central respiratory drive or entrainment. Inorder to entrain breathing, stimulation may be provided until thecentral pattern generator activates the respiration mechanisms, whichincludes those of the upper airway, in phase with the stimulationthrough various feedback mechanisms. It is believed that breathing maybe entrained when the central respiratory drive is conditioned to adaptto stimulation. When breathing is entrained, it may be possible tofurther slow respiration rate or the respiration cycle length so that itis longer than the intrinsic length 1320.

Some methods for controlling breathing are described for example in U.S.application Ser. No. 10/966,474, filed Oct. 15, 2004 and incorporatedherein by reference.

Referring to FIGS. 14A and 14B inspiration flow waveforms andstimulation pulse envelope waveforms are shown corresponding to avariation of a stimulation device and method of the invention. Inaccordance with this variation, the stimulation device stimulates duringintrinsic breaths 1411, 1412, 1413 to provide resulting breaths 1421,1422, 1423. The intrinsic breaths occur at a rate B1 as illustrated inFIG. 14A. The first stimulation 1451 is applied at a delay D1 from theonset of intrinsic breath 1411. The next stimulation 1452 is provided ata delay D2 from the onset of intrinsic breath 1412 and the subsequentstimulation pulse 1453 is provided at a delay D3 from the onset ofintrinsic breath 1413. The time between the first and second stimulation1451 and 1452 is T_(1+Δ) a while the time between the second and thirdstimulation 1452 and 1453 is T₁, i.e., shorter. Thus stimulation isprovided gradually closer and closer to the onset of stimulation togently take over breathing with stimulation at least in part duringintrinsic inspiration. The stimulation 1453 is essentially synchronouswith the start of the intrinsic inspiration 1413, to create theresulting breath 1423. Stimulation may be delivered at this rate for aperiod of time. Then the next stimulus 1454 is delivered at a ratefaster than normal at a respiration cycle length timed to thereby elicitpaced breath 1424. The next stimulus 1455 is delivered at the intervalT2, to induce another paced breath 1425, and this may be continued forsome time in order to control breathing. This may lead to theentrainment of the central respiratory control system. Also, rate may beincreased gradually until no intrinsic breaths occur between the pacedbreaths. When control of respiratory rate is achieved (and possiblyentrainment), if a slowing of the breathing rate is desired, the pacingrate can be decreased gradually as shown schematically in the Figure bystimuli delivered at a cycle length of T2+x, followed by T2+2x, inducingpaced breaths 1426 and 1427. It is believed that if entrained, ifdesired, the stimulation rate may bring the respiration rate slower thanthe intrinsic rate and tidal volume may be manipulated. After a periodof time or after breathing has been controlled as desired, the intrinsicbreathing may be allowed to resume, for example, as shown with breath1418. The patient may be weaned off stimulation, for example, asdescribed herein.

In accordance with another aspect of the invention, the phrenic nerve ordiaphragm may be stimulated using the low level stimulation as describedherein, through an OSA event after obstructive sleep apnea event hasoccurred

The stimulation described or shown herein may be comprised of severalstimulation parameters. For example a burst of pulses may form a squarepulse envelope or may ramp up or down in amplitude or a combinationthereof. The frequencies may vary or may be varied depending upon adesired result. In accordance with one embodiment, the burst frequencyranges between 5-500 Hz and more preferably between 20-50 Hz. However,other frequency ranges may be used as desired. Low level pulses orcontinuous stimulation may comprise stimulation at about 8 mA or less ormay be determined on a case-by-case basis. However, other amplitudes andfrequencies may be used as desired. The stimulation may be monophasic ormay be biphasic. Stimulation may be provided in response to sensingrespiration or other parameters. Alternatively, stimulation may beprovided periodically or during specific times, for example duringsleep, during sleep stage transitions, or during non-REM sleep.

Stimulation may also be slowly phased out. That is the patients may beweaned from stimulation slowly. In general, when paced breathing isongoing, and the therapy is to be stopped, it may be beneficial to weanthe patient off the therapy to avoid creating apnea that may lead toobstructions or arousals. Weaning off would involve a gradual decreasein rate, until an intrinsic breath is detected. Once an intrinsic breathis detected, the device would discontinue pacing and would return tomonitoring mode. An example of a protocol for weaning a patient off fromstimulation is described, for example, in U.S. application Ser. No.10/686,891 filed Oct. 15, 2003. Other variations of weaning patients offare also possible.

FIG. 15 is a flow chart illustrating operation of a system or device inaccordance with the invention. An implanted device is initialized duringan initialization period 1510. During the initialization period, amongother things, the thresholds may be set up for triggering or inhibitingtherapy. The thresholds may be set up by observing patient breathingover time. Therapy modalities may also be chosen, for example by testingvarious stimulation protocols to optimize therapy. For example,information obtained from one or more breaths can be used to set pacingparameters for subsequent therapies. Examples of data that can beobtained from one or a series of breaths include: rate, tidal volume,inspiration duration, flow parameters, peak flow, and/or duty-cycle. Inthe case of paced breathing therapies or breathing control (and possibleentrainment), the rate of intrinsic breathing could be measured, andthen paced breathing could be delivered, for example, at a faster ratethan the measured rate. As another example, one could measure theinspiration duration of previous intrinsic breaths, and induce a breathto create an inspiration duration longer (or shorter) than the previousintrinsic breaths. During initialization or when updating the device,test stimulation signals and measured responses may be used to determineappropriate stimulation parameters.

During operation, the therapy is turned on 1520. This may be doneautomatically or manually. Therapy is delivered 1530 as is determined tobe appropriate for a particular patient in accordance with one or moreprotocols, for example as described herein.

While the invention has been described with respect to treatingobstructive sleep apnea, various aspects of the invention are notlimited to use in obstructive sleep apnea patients. The varioustechniques for controlling breathing as disclosed herein may be used inother therapeutic applications where controlling breathing is desired,for example in various breathing related disorders.

For example, stimulating breathing during intrinsic inspiration may beuseful in any treatment involving control of breathing. Stimulatingduring intrinsic inspiration may be used as a technique to graduallybegin to control or manipulate breathing parameters such as breathingrate, inspiration duration and tidal volume. Simulation during intrinsicbreathing may be used with a number of breathing control protocols toinitiate control of breathing, e.g., to gradually take over or toentrain breathing and to gradually control or manipulate breathingparameters.

The various techniques used to increase functional residual capacitymaybe used in connection with any therapy where an increase infunctional residual capacity results in a desired benefit.

Likewise, therapy described herein that stiffen the upper airway mayalso be used in any therapy for a breathing related disorder where theeffects of improving upper airway patency are beneficial.

Similarly the techniques for controlling or entraining breathing asdescribed herein may be used in other therapeutic applications wherecontrolling or entraining breathing is desired.

Similarly, techniques for creating ventilatory stability as describedherein may be used in other therapeutic application where stabilizationis beneficial.

Stimulation may be provided at various times during sleep or varioussleep stages or sleep transitions, including but not limited to, forexample: prior to sleep, at sleep onset, upon detection of droppingtidal volume, upon detection of transition into REM or non-REM or duringREM or non-REM sleep, or upon changes in breathing patterns, includingbut not limited to breathing rate.

The various stimulation protocols described herein may be combined in avariety of manners to achieve desired results.

1. A method of treating an obstructive airway disorder in a patient whohas been diagnosed with an obstructive airway disorder comprising thestep of: monitoring an indication of respiratory activity from tissueinternally within the patient via at least one electrode; detecting viaa processor for a characteristic indicative of an obstructiverespiratory event from the respiratory activity; and, upon detection ofthe characteristic providing electrical stimulation to the diaphragm orphrenic nerve tissue at least to an end of exhalation where a waveformof the stimulating signal for controlling exhalation is adjusted inresponse to the sensed parameter whereby a supplemental lung volume ispreserved to thereby mitigate an obstructive disorder.
 2. The method ofclaim 1 wherein the step of providing stimulation to manipulate thediaphragm comprises providing stimulation during intrinsic breathing. 3.The method of claim 1 wherein the step of stimulating comprisesproviding stimulation to create a lung volume bias.
 4. The method ofclaim 1 wherein the step of providing stimulation comprises manipulatingthe diaphragm to increase functional residual capacity.
 5. The method ofclaim 1 wherein the step of providing stimulation comprises manipulatingthe diaphragm to increase lung volume during at least a portion of anexhalation cycle.
 6. The method of claim 1 wherein the step of providingstimulation comprises manipulating the diaphragm to increase lung volumeduring at least a portion of an end portion of an exhalation cycle. 7.The method of claim 1 wherein the step of providing stimulationcomprises manipulating the diaphragm to increase lung volume immediatelyprior to a subsequent inspiration cycle.
 8. The method of claim 1wherein the step of providing stimulation comprises providing astimulation signal whereby an intrinsic breath may occur during thestimulation signal.
 9. The method of claim 1 wherein the step ofproviding stimulation comprises manipulating the diaphragm to increaseupper airway patency.
 10. The method of claim 1 wherein the step ofproviding stimulation comprises providing a stimulation for a durationgreater than the duration of one respiratory cycle.
 11. The method ofclaim 1 wherein the step of manipulating breathing comprises the step ofmanipulating an exhalation portion of a respiration cycle.
 12. Themethod of claim 11 wherein the step of manipulating an exhalationportion comprises the step of stimulating during the exhalation portionof the respiration cycle.
 13. The method of claim 11 wherein the step ofproviding stimulation comprises providing a stimulation configured tomanipulate the duration of an exhalation portion of a respiration cycle.14. The method of claim 11 wherein the step of providing a stimulationcomprises providing a stimulation configured to manipulate a ratio ofthe duration of an exhalation portion of a respiration cycle withrespect to an inspiration portion of the respiration cycle.
 15. Themethod of claim 1 wherein the step of stimulating tissue associated withrespiration comprises providing a stimulation configured to manipulatethe duration of an inspiration portion of a respiration cycle.
 16. Themethod of claim 15 wherein the step of manipulating the duration of aninspiration cycle comprises increasing the duration of an inspirationcycle.
 17. The method of claim 1 wherein the step of stimulating tissueassociated with respiration comprises stimulating during an inspirationcycle of an intrinsic breath of a patient.
 18. The method of claim 17wherein the step of stimulating tissue associated with respirationcomprises providing stimulation to normalize tidal volume.
 19. Themethod of claim 1 wherein the step of stimulating the tissue associatedwith respiration comprises controlling breathing of the patient.
 20. Themethod of claim 19 wherein the step of controlling breathing comprisesentraining breathing.
 21. The method of claim 19 wherein the step ofcontrolling breathing comprises controlling breathing for apredetermined period.
 22. The method of claim 19 wherein the step ofcontrolling breathing comprises increasing tidal volume of a breath withrespect to a baseline normal tidal volume.
 23. A method of claim 1further comprising: sensing at least one respiration parameter.
 24. Themethod of claim 23 further comprising the step of coordinating thestimulation with the at least one sensed respiration parameter.
 25. Themethod of claim 24 wherein the step of coordinating the stimulationcomprises stimulating during an end portion of an exhalation portion ofa respiration cycle.
 26. The method of claim 24 wherein the step ofcoordinating the stimulation comprises synchronizing stimulation with aportion of an intrinsic breath.
 27. The method of claim 24 wherein thestep of coordinating the stimulation comprises stimulating during atleast a portion of a respiration cycle.
 28. The method of claim 23wherein the step of sensing at least one respiration parameter comprisessensing at least one indicator preceding onset of an obstructiverespiratory event.
 29. The method of claim 28 wherein the step ofsensing a respiration parameter comprises sensing an erratic breathingcharacteristic.
 30. The method of claim 23 wherein the step of sensingat least one indicator comprises sensing a tidal volume correlatedsignal of a patient below a predetermined threshold.
 31. The method ofclaim 23 wherein the step of coordinating electrical stimulation withthe at least one respiration parameter comprises timing the stimulationwith respect to said at least one parameter.
 32. An obstructive airwaydisorder treatment device comprising: an electrical stimulatorconfigured to provide an electrically stimulating signal to diaphragm orphrenic nerve tissue associated with respiration, to elicit a diaphragmresponse; a sensor configured to sense at least one respirationparameter in electrical communication with the electrical stimulator; aprocessor configured to communicate with the sensor and programmed tocoordinate the electrically stimulating signal with the at least onesensed respiration parameter during natural intrinsic respiration by andfurther programmed to detect for a characteristic indicative of anobstructive respiratory event from the sensed respiration, and, whereinthe processor is also programmed to actuate the electrical stimulator toprovide the electrically stimulating signal to the tissue at least to anend of exhalation where a waveform of the stimulating signal forcontrolling exhalation is adjusted in response to the sensed parameterwhereby a supplemental lung volume is preserved.
 33. The device of claim32 wherein the electrical stimulator is configured to providestimulation to manipulate the diaphragm to increase lung volume duringat least a portion of an exhalation cycle.
 34. The device of claim 32wherein the electrical stimulator is configured to manipulate thediaphragm to increase lung volume immediately prior to a subsequentinspiration cycle.
 35. The device of claim 32 wherein the electricalstimulator is configured to manipulate the diaphragm whereby anintrinsic breath may occur during the stimulation signal.
 36. The deviceof claim 32 wherein the electrical stimulator is configured tomanipulate the diaphragm to thereby increase upper airway patency. 37.The device of claim 32 wherein the electrical stimulator is configuredto manipulate the diaphragm for a duration greater than the duration ofone respiratory cycle.
 38. An obstructive airway disorder treatmentdevice comprising: an electrical stimulator configured to provide anelectrically stimulating signal to diaphragm or phrenic nerve tissueassociated with respiration, to elicit a diaphragm response; a sensorconfigured to sense at least one respiration parameter in electricalcommunication with the electrical stimulator; a processor configured tocommunicate with the sensor and programmed to coordinate theelectrically stimulating signal with the at least one sensed respirationparameter during natural intrinsic respiration by a and furtherprogrammed to detect for a characteristic indicative of an obstructiverespiratory event from the sensed respiration, and, wherein theprocessor is also programmed to actuate the electrical stimulator toprovide the electrically stimulating signal to the tissue at least to anend of exhalation where a waveform of the stimulating signal forcontrolling exhalation is adjusted in response to the sensed parameterwhereby a supplemental lung volume is preserved.
 39. An obstructiveairway disorder treatment device comprising: an obstructive respiratorydisorder detector configured to detect at least one respirationparameter associated with an airway obstruction; a processor configuredto communicate with the detector and is programmed to coordinate anelectrical stimulation with the at least one respiration parameter; anelectrical stimulator actuated by the processor and configured to beprogrammed to stimulate diaphragm or phrenic nerve tissue associatedwith respiration to elicit a diaphragm response at least to an end ofexhalation where a waveform of the stimulating signal for controllingexhalation is adjusted in response to the sensed parameter whereby asupplemental lung volume is preserved, wherein the electrical stimulatoris further configured to be programmed with a stimulation protocol; anda responsive element configured to respond to detection of the at leastone respiration parameter, with electrical stimulation according to theprotocol.
 40. The device of claim 39 wherein the protocol is configuredto increase functional residual capacity.
 41. The device of claim 39wherein the protocol is configured to improve upper airway patency. 42.The device of claim 39 wherein the protocol comprises an exhalationmanipulation protocol configured to manipulate exhalation to increasegas exchange through the lung.
 43. The device of claim 42 wherein theexhalation manipulation protocol comprises a stimulation protocolconfigured to provide increase lung volume during an exhalation portionof a respiration cycle.
 44. The device of claim 39 wherein the protocolcomprises an entrainment protocol configured to control breathing. 45.An obstructive airway disorder treatment device comprising: anelectrical stimulator configured to provide an electrically stimulatingsignal to diaphragm or phrenic nerve tissue associated with respiration,to elicit a diaphragm response to preserve a supplemental lung volume atleast to an end of exhalation; a sensor configured to sense at least onerespiration parameter in electrical communication with the electricalstimulator; a processor configured to communicate with the sensor andprogrammed to coordinate the electrically stimulating signal with the atleast one sensed respiration parameter during natural intrinsicrespiration by a and further programmed to detect for a characteristicindicative of an obstructive respiratory event from the sensedrespiration, and; wherein the processor is also programmed to actuatethe electrical stimulator to provide the electrically stimulating signalto the tissue at least to an end of exhalation where a waveform of thestimulating signal for controlling exhalation is adjusted in response tothe sensed parameter whereby a central respiratory drive is entrained.